Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000227140 | SCV000283556 | uncertain significance | Fanconi anemia | 2016-02-23 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with leucine at codon 968 of the FANCA protein (p.Ser968Leu). The serine residue is moderately conserved and there is a large physicochemical difference between serine and leucine. This variant is present in population databases (rs779162871, ExAC 0.01%) but has not been reported in the literature in individuals with a FANCA-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). However, the leucine amino acid residue is found at this position in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Counsyl | RCV000673348 | SCV000798537 | uncertain significance | Fanconi anemia, complementation group A | 2018-03-13 | criteria provided, single submitter | clinical testing |